1. Field of the Invention
This invention concerns mycophenolic acid derivatives as agents in the treatment of rheumatoid arthritis.
2. Previous Disclosures
Rheumatoid arthritis has been treated with a variety of compounds representing many structural classes, including, for example, corticosteroids, aspirin and related compounds, derivatives of arylacetic and arylpropionic acids, relatives of phenylbutazone, gold salts and penicillamine and its derivatives. However, no representative of any of these classes of compounds is regarded as ideal.
Mycophenolic acid is a weakly-active antibiotic found in the fermentation broth of Pencillium brevi-compactum. It has now been discovered that certain mycophenolic acid derivatives and related compounds are useful as agents in the treatment of rheumatoid arthritis.
Compounds somewhat structurally similar to the novel compounds of the present invention (compounds illustrated by Formula II as defined herein) are described in U.S. Pat. Nos. 3,705,894; 3,853,919; 3,868,454; 3,880,995, in Japanese Patent No. J 57024380, in the J. Antibiot., 29(3), 275-85, 286-91 (1976), and in Cancer Research, 36(8), 2923-7 (1976). The disclosed compounds are described as having anti-tumour, immunosuppressive, anti-viral, anti-arthritic and anti-psoriatic activities.
The present invention includes the discovery that the family of compounds illustrated by Formula I and as defined herein are active in biological models of chronic inflammatory diseases, including models of rheumatoid arthritis in mammals. While many of these compounds are disclosed elsewhere, their usefulness in treating rheumatoid arthritis was not previously known. Compounds similar to or included in Formula I are described in U.S. Pat. Nos. 3,705,894, 3,777,020, and 3,868,454, Japanese Kokai Nos. 57/183776, 57/183777, and 48/86860, South African Application No. 68/4959, Great Britain Patent No. 1261060, Belgian Patent No. 815330, and West German Patent No. 2237549.